Finding the gene for a female attack.

For more than 40 years, scientists have known that men and women are not created equal--immunologically speaking, that is.

Whether one views it as females attacking males or as a biological favoritism toward men, the fact is that men's bodies accept donor organs from women while women's bodies reject organs from men. Scientists speculated that a male specific antigen--a protein that exists in all cells of a man's body, but in none of a woman's--caused this incompatibility.

Over the years, however, this putative protein--designated the H-Y antigen--remained elusive. A team of researchers from Britain, the United States, and France now reports finding the gene for it on the Y chromosome. "The finding allows us to examine for the first time this male-female difference," says study collaborator Colin E. Bishop at Baylor College of Medicine in Houston.

Scientists first found evidence for the H-Y antigen when they transplanted skin between members of a highly inbred strain of laboratory mice. Apart from every males' distinctive Y chromosome, mice of both sexes were genetically identical. Males accepted transplanted skin from both males and females, but the females' immune systems slowly geared up to reject transplants from males.

Except for identical twins, humans aren't genetic duplicates so physicians prescribe drugs to stop any tissue differences from causing rejection. As a result, women's bodies accept donor organs from men.

Although drugs prevent transplant rejections, researchers still didn't know which gene was responsible for the H-Y antigen or how this protein acted.

In the Aug. 24 Nature, the international team now reports finding on the short arm of the Y chromosome a gene called Smcy--one that functions in every male cell. This gene has a counterpart, Smcx, on the X chromosome, but researchers found that proteins produced by the two genes contain different versions of an eight-amino-acid string, or peptide. And they showed the male version could trigger the H-Y antigen rejection in female cells.

"This gene [Smcy] is conserved in humans, marsupials and mice--really in everything except cattle so far," says Bishop. Because all males have both X and Y chromosomes, the presence of Smcx helps explain why males don't reject female organs: They won't reject a protein their own bodies make.

Though the protein that the Smcy gene codes for appears to resemble one that turns other genes on, its exact function remains a mystery, Bishop notes. The researchers are looking into the gene's role in forming sperm.

Harald von Boehmer of the Basel Institute for Immunology in Switzerland writes in an accompanying article that, with current tools, the gene's function is unlikely to elude researchers for long and points out that this gene may play important roles during very early development.